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The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats

OBJECTIVE: The purpose of the present study was to evaluate the role of co-treatment of rosuvastatin (RSV) and dapagliflozin (DGZ) preconditioning in myocardium ischemia/reperfusion (I/R) injury and to further investigate the underlying mechanism. METHODS: Sprague-Dawley (SD) rats (n = 25) were divi...

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Autores principales: Gong, Lei, Wang, Xuyang, Pan, Jinyu, Zhang, Mingjun, Liu, Dian, Liu, Ming, Li, Li, An, Fengshuang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: De Gruyter 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754177/
https://www.ncbi.nlm.nih.gov/pubmed/33385063
http://dx.doi.org/10.1515/med-2021-0005
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author Gong, Lei
Wang, Xuyang
Pan, Jinyu
Zhang, Mingjun
Liu, Dian
Liu, Ming
Li, Li
An, Fengshuang
author_facet Gong, Lei
Wang, Xuyang
Pan, Jinyu
Zhang, Mingjun
Liu, Dian
Liu, Ming
Li, Li
An, Fengshuang
author_sort Gong, Lei
collection PubMed
description OBJECTIVE: The purpose of the present study was to evaluate the role of co-treatment of rosuvastatin (RSV) and dapagliflozin (DGZ) preconditioning in myocardium ischemia/reperfusion (I/R) injury and to further investigate the underlying mechanism. METHODS: Sprague-Dawley (SD) rats (n = 25) were divided into five groups randomly: (1) Sham, (2) I/R, (3) I/R + RSV (10 mg/kg), (4) IR + DGZ (1 mg/kg), and (5) I/R + RSV (10 mg/kg) + DGZ (1 mg/kg). The I/R model was induced with 30 min of left anterior descending occlusion followed by 120 min of reperfusion. RESULTS: In vivo pretreatment with RSV and DGZ, respectively, showed a significant reduction of infarction size, a significant increase in the levels of left ventricular systolic pressure, and maximal rate increase in left ventricular pressure (+dp/dt (max)), decrease in the levels of left ventricular end-diastolic pressure (LVEDP), maximal rate of decrease of left ventricular pressure (−dp/dt (max)) and activity of cardiac enzymes of creatine kinase (CK), creatine kinase MB isoenzymes (CK-MB), and hyper-tensive cardiac troponin I compared with the I/R group. H9C2 cells were exposed to hypoxia/reoxygenation to simulate an I/R model. In vitro administration of 25 µM RSV and 50 µM DGZ significantly enhanced cell viability, upregulated the expression levels of p-PI3K, p-Akt, p-mTOR, and Bcl-2, whereas it downregulated cleaved-caspase3, Bax. TUNEL assay indicated that pretreatment with RSV and DGZ decreased the apoptosis of H9C2 cells. CONCLUSION: The combination of RSV and DGZ significantly enhances the cardioprotective effects compared with RSV or DGZ alone. RSV and DGZ have the potential cardioprotective effects against I/R injury by activating the PI3K/AKt/mTOR signaling pathway.
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spelling pubmed-77541772020-12-30 The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats Gong, Lei Wang, Xuyang Pan, Jinyu Zhang, Mingjun Liu, Dian Liu, Ming Li, Li An, Fengshuang Open Med (Wars) Research Article OBJECTIVE: The purpose of the present study was to evaluate the role of co-treatment of rosuvastatin (RSV) and dapagliflozin (DGZ) preconditioning in myocardium ischemia/reperfusion (I/R) injury and to further investigate the underlying mechanism. METHODS: Sprague-Dawley (SD) rats (n = 25) were divided into five groups randomly: (1) Sham, (2) I/R, (3) I/R + RSV (10 mg/kg), (4) IR + DGZ (1 mg/kg), and (5) I/R + RSV (10 mg/kg) + DGZ (1 mg/kg). The I/R model was induced with 30 min of left anterior descending occlusion followed by 120 min of reperfusion. RESULTS: In vivo pretreatment with RSV and DGZ, respectively, showed a significant reduction of infarction size, a significant increase in the levels of left ventricular systolic pressure, and maximal rate increase in left ventricular pressure (+dp/dt (max)), decrease in the levels of left ventricular end-diastolic pressure (LVEDP), maximal rate of decrease of left ventricular pressure (−dp/dt (max)) and activity of cardiac enzymes of creatine kinase (CK), creatine kinase MB isoenzymes (CK-MB), and hyper-tensive cardiac troponin I compared with the I/R group. H9C2 cells were exposed to hypoxia/reoxygenation to simulate an I/R model. In vitro administration of 25 µM RSV and 50 µM DGZ significantly enhanced cell viability, upregulated the expression levels of p-PI3K, p-Akt, p-mTOR, and Bcl-2, whereas it downregulated cleaved-caspase3, Bax. TUNEL assay indicated that pretreatment with RSV and DGZ decreased the apoptosis of H9C2 cells. CONCLUSION: The combination of RSV and DGZ significantly enhances the cardioprotective effects compared with RSV or DGZ alone. RSV and DGZ have the potential cardioprotective effects against I/R injury by activating the PI3K/AKt/mTOR signaling pathway. De Gruyter 2020-12-11 /pmc/articles/PMC7754177/ /pubmed/33385063 http://dx.doi.org/10.1515/med-2021-0005 Text en © 2021 Lei Gong et al., published by De Gruyter http://creativecommons.org/licenses/by/4.0 This work is licensed under the Creative Commons Attribution 4.0 International License.
spellingShingle Research Article
Gong, Lei
Wang, Xuyang
Pan, Jinyu
Zhang, Mingjun
Liu, Dian
Liu, Ming
Li, Li
An, Fengshuang
The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats
title The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats
title_full The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats
title_fullStr The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats
title_full_unstemmed The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats
title_short The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats
title_sort co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the pi3k/akt/mtor signaling pathway in myocardial ischemia/reperfusion injury rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754177/
https://www.ncbi.nlm.nih.gov/pubmed/33385063
http://dx.doi.org/10.1515/med-2021-0005
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